Beta-Carotene and Lung Cancer: The Story Behind the Story

Written by Keith I Block, MD

Most of you are likely familiar with the concept of antioxidants.  Essentially, antioxidants help neutralize free radicals—those highly unstable and reactive molecules that are generated by many factors, including everyday metabolism and immune system activity against bacteria and viruses, as well as by exercise, dietary fats, pollutants, chemotherapy, radiotherapy, and inflammation.  When you have too many free radicals and too few antioxidants in your system, you have what’s called oxidative stress.  Research has shown that cancer thrives under conditions of persistent oxidative stress, which helps explain why antioxidant-rich diets appear to help stymie the development of cancer.

What you may not know, however, is that antioxidants, like all molecules, have varying levels of stability in terms of their antioxidant power.  Those that are less stable, or more labile, will function as antioxidants under certain conditions.  However, under other conditions, they can actually become oxidants – that is, generators of free radical damage. 

A good example of this Jekyll-and-Hyde character of some antioxidants comes from human studies of beta-carotene, one of the most labile of all antioxidants.  Two randomized clinical trials on beta-carotene, both involving smokers, have helped foster a widespread belief that beta-carotene, and possibly other antioxidant supplements, are harmful for people with cancer.  This belief is based on a set of erroneous assumptions, as I shall now explain.

The first clinical trial, known as the Alpha-Tocopherol Beta-Carotene Trial (ATBC), involved approximately 29,000 Finnish male smokers who had been randomly assigned to receive either beta carotene, vitamin E, both active agents, or neither, for an average of six years.  The second trial, the Carotene and Retinol Efficacy Trial (CARET), enrolled 18,000 men and women in the U.S. who were at high risk for lung cancer because of a history of cigarette smoking or occupational exposure to asbestos.  Participants in this intervention received 30 mg of beta-carotene and 25,000 IU of retinyl palmitate.

Both clinical trials found an increase in lung cancer mortality among those who took beta-carotene.  The media stories that followed were quick to cast beta-carotene (and by extension, all so-called antioxidant supplements) as not only failures in cancer prevention, but as harmful to cancer patients.  However, my response to the findings is to say that it simply isn’t realistic to suggest that beta-carotene – or any other micronutrient alone – could possibly compensate for the harmful consequences of long-term exposure to cigarette smoke or asbestos, and the resulting injury to the individual’s microenvironment.  Moreover, a history of heavy smoking and asbestos exposure would strongly suggest a profile of oxidative stress.  Laboratory research has clearly shown that beta-carotene shifts to a pro-oxidative state in a highly oxidative environment, in this case, in the context of chronic exposure to tobacco smoke.  In addition, some laboratory studies have found that a combination of cigarette smoke with high-dose beta-carotene may actually accelerate the growth of lung tumors.

More recently, epidemiologists from the University of North Carolina took a look at long-term use of individual supplements at high doses in a follow-up to the VITamins And Lifestyle (VITAL) Study.  Over 90% of the participants who developed lung cancer were smokers.  The findings, which were reported in the June 2009 issue of the American Journal of Epidemiology, led to the following conclusion: Long-term use of high doses of beta-carotene may be harmful in terms of lung cancer risk.

What about studies that did not focus on beta-carotene use in smokers?  Or studies on people who do not have high levels of oxidative stress?  To date, there have been two large clinical trials involving non-smokers—the Physicians’ Health Study and the Women's Health Study—and in these studies, beta-carotene supplements had no adverse impact!  Once again, then, beta-carotene may only be a problem in the context of smoking or other oxidative stress-promoting behavior.  In my view, the take-home lesson is that beta-carotene should only be taken in combination with a plant-based diet and broad-spectrum antioxidant supplements—and preferably only if you do not have a history of heavy smoking, drinking or asbestos exposure.

A closely related point that must be made is that most people do not actually use supplements as supplements!  By definition, “supplements” are supposed to complement a healthy diet and provide the right balance of synergists, thereby providing the terrain with the highest antioxidant power possible.  A poor diet can sabotage any supplement program, yet many people take supplements thinking that they can just go ahead and continue eating junk foods or other foods, which can actually promote degenerative disease.  This is why I strongly advocate an individualized clinical approach to the use of any nutraceutical regimen, with a whole foods dietary program at the foundation, supplementing with multi-nutrient agents.

Back to the subject of beta-carotene:  There is some laboratory research that suggests that beta-carotene may have some benefit as a single nutrient in the context of chemotherapy treatment.  Beta-carotene was found to dramatically improve the survival of animals with various tumors when the supplement was combined with a commonly used group of chemotherapy drugs known as alkylating agents.  Common examples of this class of chemo drugs include Cyclophosphamide, Melphalan, and Ifosfamide.  It will be interesting to see if these findings are eventually borne out by clinical trials. 

As far as the messaging from mass media that all antioxidants should be studiously avoided by cancer patients:  In 2007, my research staff and I conducted a systematic review of the use of antioxidants during chemotherapy, which was published in the May, 2007 issue of the peer-reviewed journal Cancer Treatment Reviews.  Our review suggested that antioxidants may, in fact, help increase survival rates, tumor response, as well as a patient’s ability to tolerate treatment.  More on this in next week’s blog.

For more information on The Block Center for Integrative Cancer Treatment, visit BlockMD.com.

Comments

[Natalie]

You made some excellent points in this article. I will look forward to read more about how antioxidants may help increase survival rates and tumor response in a patient undergoing chemo.

[Barbara]

"However, my response to the findings is to say that it simply isn’t realistic to suggest that beta-carotene – or any other micronutrient alone – could possibly compensate for the harmful consequences of long-term exposure to cigarette smoke or asbestos, and the resulting injury to the individual’s microenvironment." Yes! Definitely agree with you. We need to find a balance...there is such a thing as too much of a good thing! And thanks for the great explanation of oxidative stress!

[Mark Nelson]

This is really a fantastic explanation. This is why I have used an antioxidant supplement that does not contain beta-carotene while I was taking my chemotherapy along with a multi-vitamin and fish oil. I'm doing great now and things couldn't be better.